Posology : מינונים

4.2.    Posology and method of administration

Posology
Table 1: Adults and children ≥ 40 kg

Intermittent Administration
Infection                                              Dose to be administered 
Broncho-pulmonary infections in cystic                 100 to 150 mg/kg/day every 8 h, fibrosis                                               maximum 9 g per day1 Febrile neutropenia
Nosocomial pneumonia                                   2 g every 8 h
Bacterial meningitis
Bacteraemia*
Bone and joint infections
Complicated skin and soft tissue                       1-2 g every 8 h infections
Complicated intra-abdominal infections
Peritonitis associated with dialysis in patients on CAPD
Complicated urinary tract infections                   1-2 g every 8 h or 12 h Peri-operative prophylaxis for                         1 g at induction of anaesthesia, and a transurethral resection of prostate                    second dose at catheter removal (TURP)
Chronic suppurative otitis media
Malignant otitis externa                               1 g to 2 g every 8 h Continuous infusion
Infection                                              Dose to be administered Febrile neutropenia                                    Loading dose of 2 g followed by a Nosocomial pneumonia                                   continuous infusion of 4 to 6 g every 24 h1 Broncho-pulmonary infections in cystic                 The infusion of any unit of dissolved drug fibrosis                                               shall last no longer than 8 h (see section Bacterial meningitis                                   6.3).
Bacteraemia*
Bone and joint infections                              Therefore, following reconstitution, the Complicated skin and soft tissue                       unit dose in the infusion fluid should be infections                                             administered within 8 h, for example for 8 Complicated intra-abdominal infections                 g per day: 2 g loading dose followed by 2 Peritonitis associated with dialysis in                g continuous infusion every 8 h.
patients on CAPD
1In adults with normal renal function 9 g/day has been used without adverse effects.
*When associated with, or suspected to be associated with, any of the infections listed in section 4.1.


Table 2: Children < 40 kg
Infants and toddlers >2    Infection                   Usual dose months and children
<40 kg
Intermittent Administration

Complicated urinary         100-150 mg/kg/day in three tract infections            divided doses, maximum 6
Chronic suppurative         g/day otitis media
Malignant otitis externa
Neutropenic children        150 mg/kg/day in three divided
Broncho-pulmonary           doses, maximum 6 g/day infections in cystic fibrosis
Bacterial meningitis
Bacteraemia*
Bone and joint              100 – 150 mg/kg/day in three infections                  divided doses, maximum 6
Complicated skin and        g/day soft tissue infections
Complicated intra- abdominal infections
Peritonitis associated with dialysis in patients on CAPD
Continuous Infusion

Febrile neutropenia         Loading dose of 60-100 mg/kg
Nosocomial pneumonia        followed by a continuous
Broncho-pulmonary           infusion 100-200 mg/kg/day,
infections in cystic        maximum 6 g/day fibrosis
Bacterial meningitis
Bacteraemia*
Bone and joint infections
Complicated skin and soft tissue infections
Complicated intra- abdominal infections
Peritonitis associated with dialysis in patients on CAPD
Neonates and infants ≤     Infection                   Usual dose
2 months
Intermittent Administration
Most infections              25-60 mg/kg/day in two divided doses1
1
In neonates and infants ≤ 2 months, the serum half life of ceftazidime can be three to four times that in adults.
*Where associated with, or suspected to be associated with, any of the infections listed in section 4.1.



Paediatric population
The safety and efficacy of CEFTAZIDIME-VIT 2 G administered as continuous infusion to neonates and infants ≤ 2 months has not been established.

Elderly
In view of the age related reduced clearance of ceftazidime in elderly patients, the daily dose should not normally exceed 3 g in those over 80 years of age.

Hepatic impairment
Available data do not indicate the need for dose adjustment in mild or moderate liver function impairment. There are no study data in patients with severe hepatic impairment (see also section 5.2). Close clinical monitoring for safety and efficacy is advised.

Renal impairment
Ceftazidime is excreted unchanged by the kidneys. Therefore, in patients with impaired renal function, the dosage should be reduced (see also section 4.4).

An initial loading dose of 1 g should be given. Maintenance doses should be based on creatinine clearance:

Table 3: Recommended maintenance doses of CEFTAZIDIME-VIT 2 G in renal impairment – intermittent infusion

Adults and children ≥ 40 kg

Creatinine        Approx. serum               Recommended unit dose of                  Frequency of dosing clearance           creatinine               CEFTAZIDIME-VIT 2 G (g)                         (hourly) ml/min           µmol/l(mg/dl)
50-31               150-200                                   1                                   12 (1.7-2.3)
30-16              200-350                                   1                                   24 (2.3-4.0)
15-6               350-500                                   0.5                                 24 (4.0-5.6)
<5                  >500                                    0.5                                 48 (>5.6)

In patients with severe infections the unit dose should be increased by 50% or the dosing frequency increased. In children the creatinine clearance should be adjusted for body surface area or lean body mass.

Children < 40 kg

Creatinine           Approx. serum                Recommended                    Frequency of dosing clearance             creatinine*             individual dose mg/kg                   (hourly) (ml/min)**           µmol/l (mg/dl)                body weight
50-31               150-200                          25                                  12 (1.7-2.3)
30-16              200-350                             25                               24 (2.3-4.0)
15-6               350-500                            12.5                              24 (4.0-5.6)
<5                 >500                             12.5                              48 (>5.6)
* The serum creatinine values are guideline values that may not indicate exactly the same degree of reduction for all patients with reduced renal function.
** Estimated based on body surface area or measured.

Close clinical monitoring for safety and efficacy is advised.
Table 4: Recommended maintenance doses of CEFTAZIDIME-VIT 2 G in renal impairment – continuous infusion

Adults and children ≥ 40 kg

Creatinine clearance       Approx. Serum creatinine              Frequency of dosing (hourly) (ml/min)                   µmol/l (mg/dl)
50-31                        150-200                      Loading dose of 2 g followed (1.7-2.3)                        by 1 g to 3 g /24 hours
30-16                       200-350                       Loading dose of 2 g followed (2.3-4.0)                            by 1 g /24 hours
≤ 15                        > 350                                Not evaluated (>4.0)
Caution is advised in dose selection. Close clinical monitoring for safety and efficacy is advised.

Children < 40 kg

The safety and effectiveness of CEFTAZIDIME-VIT 2 G administered as continuous infusion in renally impaired children < 40 kg has not been established, Close clinical monitoring for safety and efficacy is advised.

If continuous infusion is used in children with renal impairment, the creatinine clearance should be adjusted for body surface area or lean body mass.

Haemodialysis
The serum half-life during haemodialysis ranges from 3 to 5 h.

Following each haemodialysis period, the maintenance dose of ceftazidime recommended in tables 3 & 4 should be repeated.

Peritoneal dialysis
Ceftazidime may be used in peritoneal dialysis and continuous ambulatory peritoneal dialysis (CAPD).

In addition to intravenous use, ceftazidime can be incorporated into the dialysis fluid (usually 125 to 250 mg for 2 liters of dialysis solution).

For patients in renal failure on continuous arterio-venous haemodialysis or high-flux haemofiltration in intensive therapy units: 1 g daily either as a single dose or in divided doses.
For low-flux haemofiltration, follow the dose recommended under renal impairment.

For patients on veno-venous haemofiltration and veno-venous haemodialysis, follow the dosage recommendations in tables 5 & 6 below.

Table 5: Continuous veno-venous haemofiltration dose guidelines

Residual renal             Maintenance dose (mg) for an ultrafiltration rate (ml/min) of1: function
(creatinine                    5                     16.7        33.3               50 clearance ml/min)
0                     250                    250         500                500 5                     250                    250         500                500 10                     250                    500         500                750 15                     250                    500         500                750 20                     500                    500         500                750
1 Maintenance   dose to be administered every 12 h.

Table 6: Continuous veno-venous haemodialysis dose guidelines

Residual                   Maintenance dose (mg) for a dialysate in flow rate of 1: renal                           1.0 liter/h                         2.0 liter/h function               Ultrafiltration rate (liter/h)      Ultrafiltration rate (liter/h) (creatinine           0.5           1.0            2.0    0.5           1.0            2.0 clearance in ml/min)
0              500            500               500      500       500          750 5              500            500               750      500       500          750 10              500            500               750      500       750         1000 15              500            750               750      750       750         1000 20              750            750              1000      750       750         1000
1Maintenance   dose to be administered every 12 h.

Method of administration

The dose depends on the severity, susceptibility, site and type of infection and on the age and renal function of the patient.

CEFTAZIDIME-VIT 2 G should be administered by intravenous injection or infusion.
CEFTAZIDIME-VIT 2 G solutions may be given directly into the vein or introduced into the tubing of a giving set if the patient is receiving parenteral fluids. The standard recommended route of administration is by intravenous intermittent injection or intravenous continuous infusion.